Various analogs of ethoxzolamide and methazolamide have been diagnosed and will be synthesized for the purpose of promoting penetration and distribution into the eye from a topically applied dose. It is hypothesized that carbonic anhydrase inhibitors are not effective in lowering intraocular pressure when administered topically to the eye because of an inadequate rate of tissue penetration. Each synthesized analog in this study will be compared and structurally modified using in-vitro parameters (i.e., solubility, partitioning, carbonic anhydrase inhibition, pka and excised cornea permeability coefficients). Selected analogs will then be administered intravenously to rabbits in threshold doses and, in addition, will be given in various doses topically to the rabbit eye. A comparison of tissue levels from both routes of administration will indicate the potential for achieving effective tissue levels of carbonic anhydrase inhibitors from topical dosing. Pressure lowering efficacy will be evaluated in drug sensitive rabbits using a masked controlled trial.